Melanoma is a rare, albeit potentially highly aggressive malignant tumor of melanocytes. Melanomas can spread quickly beyond the primary site at which they developed, they are highly curable if discovered and treated early. Primary tumor thickness has been considered to be the most influential prognostic factor in melanoma patients. No previous studies have reported an association between single nucleotide polymorphisms(SNPs) and tumor thickness or the biological roles of SNPs in melanoma progression. To determine whether common genetic variants that influence tumor thickness affect melanoma prognosis and also elucidate the molecular mechanism of disease progression, we propose to perform a coordinated genome-wide SNP analysis together with targeted gene expression analysis. We will test our hypothesis through the following aims: 1)To determine common genetic variants associated with Breslow tumor thickness among melanoma patients using genome-wide SNP analysis; 2)To examine expression patterns of candidate genes identified in Aim 1 using patient tissues with varying tumor thickness categories, via mRNA expression analysis and immunohistochemistry; and 3)To predict risk of melanoma recurrence and death on the basis of the SNPs identified in Aim 1. Identifying common genetic determinants of tumor thickness may provide new insights into prognosis in melanoma. Our findings will have a significant impact on the staging of melanoma and outcome prediction for melanoma patients who are at risk for relapse and metastasis, and provide clues for the development of new molecular targeted therapies.